The broad objectives are to obtain mutants of E.coli defective in each of the proteins involved in the reduction of ribonucleotides to deoxyribonucleotides. Mutants in B1 protein will be characterized to determine whether the mutations affect regulation of enzyme activity by the various effectors, or whether enzyme activity is reduced irrespective of the effectors present. Mutants in thioredoxin and thioredoxin reductase will be useful in determining whether these proteins are involved only in ribonucleotide reduction, or whether they also play a role in other reactions in E. coli e.g. sulfate reduction. The control of ribonucleotide reductase synthesis will be studied by varying conditions for derepression of B1 and B2 proteins in order to determine what nucleotides may be involved in repression of enzyme synthesis, and whether B1 and B2 are derepressed coordinately.